title: HMGB factors are required for posterior digit development through integrating signaling pathway activities.
abstract: The chromatin factors Hmgb1 and Hmgb2 have critical roles in cellular processes, including transcription and DNA modification. To identify the function of Hmgb genes in embryonic development, we generated double mutants of Hmgb1;Hmgb2 in mice. While double null embryos arrest at E9.5, Hmgb1(-/-) ; Hmgb2(+/-) embryos exhibit a loss of digit5, the most posterior digit, in the forelimb. We show that Hmgb1(-/-) ; Hmgb2(+/-) forelimbs have a reduced level of Shh signaling, as well as a clear downregulation of Wnt and BMP target genes in the posterior region. Moreover, we demonstrate that hmgb1 and hmgb2 in zebrafish embryos enhance Wnt signaling in a variety of tissues, and that double knockdown embryos have reduced Wnt signaling and shh expression in pectoral fin buds. Our data show that Hmgb1 and Hmgb2 function redundantly to enhance Wnt signaling in embryos, and further suggest that integrating Wnt, Shh, and BMP signaling regulates the development of digit5 in forelimbs.
authors.affiliation: Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Junji
authors.initials: J
authors.lastname: Itou
authors.forename: Noboru
authors.initials: N
authors.lastname: Taniguchi
authors.forename: Isao
authors.initials: I
authors.lastname: Oishi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kawakami
authors.forename: Martin
authors.initials: M
authors.lastname: Lotz
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kawakami
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D005121:Extremities / Q000196:embryology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D024002:HMGB Proteins / Q000235:genetics / Q000378:metabolism*; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism; D024261:HMGB2 Protein / Q000235:genetics / Q000378:metabolism; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008817:Mice, Mutant Strains; D008954:Models, Biological; D011247:Pregnancy; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish
chemical_list: D019485:Bone Morphogenetic Proteins; D024002:HMGB Proteins; D024243:HMGB1 Protein; D024261:HMGB2 Protein; D053823:Hedgehog Proteins; C465570:Shh protein, mouse; D051153:Wnt Proteins